In addition to functioning in barrier defense, AMPs may facilitate the wound-healing process. Clinical trials are necessary to assess their efficacy and safety as therapeutic agents. (More information)

Too low and too high levels of certain antimicrobial peptides (AMPs) (see Wound healing) have been associated with various skin disorders, such as psoriasis, atopic dermatitis, and rosacea (2, 5, 6). This article focuses on the roles of peptides in healthy skin, however, and such skin disorders are not discussed.

Product formulation can greatly influence the stability of the bioactive peptide. Palmitoyl-KTTKS (Lysine-Threonine-Threonine-Lysine-Serine) was measured in six different anti-wrinkle creams using a mass-spectrometry analytical procedure (8). Pal-KTTKS content ranged from 99.9% to only 23.5% of the initial, expected value. Although composition details were not included in the analysis, it is clear that cosmetic additives can significantly influence the availability of bioactive peptide.

Deficiency

The application of peptides to skin health is exclusively as topical agents. Bioactive peptides are not dietary factors and have no dietary requirements.

Bioactive peptides can also inhibit melanin synthesis and are under investigation for the treatment of hyperpigmentation in the skin (see Other functions).

Photoaging

The C-terminal fragment (residues 197-241) of procollagen I is capable of stimulating the production of type I and type III Hilfiger Tommy Hilfiger Women Women Tommy Tommy Hilfiger Tommy Tommy Hilfiger Tommy Women Hilfiger Women Women 5qXqp and fibronectin in cultured human fibroblasts(10). KTTKS (Lysine-Threonine-Threonine-Lysine-Serine), a peptide derived from the procollagen I C-terminus, represents the minimum sequence necessary to stimulate ECM synthesis in vitro(11). The effect of the synthetic, lipid-conjugated peptide palmitoyl-KTTKS (pal-KTTKS) on photoaged facial skin was evaluated in a double-blind, placebo-controlled study (12). Ninety-three Caucasian women (aged 35-55 years) applied control moisturizer or pal-KTTKS moisturizer (3 ppm) to the left or right side of their faces twice daily for 12 weeks. Computer image analysis revealed that topical pal-KTTKS did not cause skin irritation and induced qualitative improvements in fine line and wrinkling scores compared to placebo. Another synthetic peptide, GEKG (Glycine-Glutamate-Lysine-Glycine), was evaluated for its ability to influence ECM production in vitro and in vivo(13). In vitro, GEKG significantly induced the expression of procollagen I, hyaluronic acid, and fibronectin mRNA and induced secretion of procollagen I from human fibroblasts. These findings were corroborated in a small double-blind, placebo-controlled study in ten volunteers (mean age, 48.2 years) (13). Topical GEKG (50 ppm) applied daily for eight weeks increased the production of procollagen I, hyaluronic acid, and fibronectin in biopsied buttock skin and improved measures of skin elasticity compared to placebo. A follow-up placebo-controlled study in 60 volunteers compared the effect of topical GEKG (10 and 100 ppm) to pal-KTTKS (50 ppm) on facial skin elasticity. After eight weeks of twice daily application, skin roughness, volume, and elasticity were significantly improved by both peptides compared to placebo, though to the greatest extent following 100 ppm GEKG treatment.

Wound healing

Antimicrobial peptides

Cathelicidins, defensins, and dermicidins comprise the major families of antimicrobial peptides (AMPs) in the skin (2, 3). All require extracellular proteolytic processing in order to generate activated AMPs (5). For example, the human cathelicidin gene encodes the inactive precursorprotein, hCAP18, which is cleaved by proteases in order to generate the 37-amino acid AMP known as LL-37 (5) (see the article on Vitamin D and Skin Health). In addition to LL-37, other peptide fragments cleaved from the C-terminus of cathelicidin function as AMPs in the skin (14). In response to infection or injury, AMPs accumulate due to increased synthesis by keratinocytes and deposition from recruited neutrophils(15). AMPs directly kill microbes by disrupting microbial cell membranes and modulate host inflammatory, innate, and adaptive immune responses (16).

GHK-Cu

GHK (glycyl-L-histidyl-L-lysine) is a fragment of the α chain of Hilfiger Tommy Hilfiger Women Women Tommy Tommy Hilfiger Tommy Tommy Hilfiger Tommy Women Hilfiger Women Women 5qXqp and has a high affinity for copper (2). Copper is a cofactor for lysyl oxidase, an enzyme involved in collagen synthesis, and superoxide dismutase (SOD), an antioxidant enzyme that neutralizes free radicals (see the article on Copper). Experiments performed in vitro and in animals demonstrate that GHK alone and as a carrier peptide for copper (GHK-Cu) modulate various aspects of the wound-healing process, including chemoattraction of immune cells, angiogenesis, and collagen synthesis (21-24). Although GHK is implicated in wound healing, there are few data from human trials. In a small study, patients (N=13) who underwent laser resurfacing of facial skin were randomized to receive a post-treatment topical regimen with or without GHK-Cu for 12 weeks (25). Computerized image analysis and clinical evaluation revealed no statistically significant differences between the groups for earlier resolution of erythema, wrinkling, and overall skin quality.

Other functions

Hyperpigmentation

The KEK motif is present in the antimicrobial peptide derived from cathelicidin (LL-37) (see the article on Vitamin D and Skin Health). Another KEK-containing peptide, PKEK (Proline-Lysine-Glycine-Lysine), exerts skin-whitening effects in vitro and in vivo(26). In 10 volunteers, pretreatment with PKEK (40 ppm) daily for four weeks reduced UVB-induced gene expression of several keratinocyte-derived pigmentation-inducing factors in biopsied buttock skin compared to control sites on the same individuals (26). In three separate, small, double-blind, placebo-controlled studies, daily application of topical PKEK in combination with the skin whitener, sodium ascorbyl phosphate (SAP), for six to eight weeks enhanced the fading of skin pigment spots compared to either agent alone (26).

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